We report here seven COVID-19 patients who developed similar symptoms, i.e., myoclonus. These cases were consulted with two of authors (MR and ME) in a referral center for movement disorders. The cases 1, 3, and 4 were reported from centers where two of the authors work and managed them (MB and MJ). Cases 2 and 5 were managed in the hospitals where two of the authors are practicing (MM and MZ, respectively). The 6th patient was referred for treatment to ME and MR. The 7th patient was recently managed by our colleague; FM, ME, and MR were consulted on this case. All patients gave their informed consent prior to their inclusion in the study. Patient’s characteristics and their disease-related information are summarized in Table 1.
Case 1. A 51-year-old male health-care staff (nurse) presented with sore throat, back pain, anorexia, and mild dyspnea. There was no leukocytosis, lymphopenia, or increment in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). The chest CT revealed few peripheral patchy ground-glass opacities (Fig. 1). Brain CT was normal. His nasopharyngeal swab sample RT-PCR test result for COVID-19 was positive. He was treated with non-steroidal anti-inflammatory drugs (piroxicam IM) for myalgia, hydroxychloroquin, and azithromycin. Two weeks after initial symptoms, he noticed tremor-like jerky movements in his hands which progressively increased in severity and became worse with intentional movements. After several days, his legs and voice were involved with tremor and he noticed oscillopsia. His jerky movements diagnosed as generalized stimulus sensitive and action myoclonus, treated with clonazepam 0.5 mg qhs and levetiracetam 500 mg bid. His extra ocular movements were fragmented during pursuit movements intermixed with jerky oscillatory movements of eyes in all directions (opsoclonus) and corrective rapid head movements. There was slightly truncal ataxia (wide-based gait) more prominent during tandem walking (Online Resource 1). Based on these symptoms, parainfectious OMS was presumed and IVIG was started to a total dose of 150 g (2 g/kg). The improvement of abnormal movements was noticeable after 1 week of IVIG initiation and markedly improved 3 weeks after treatment (Online Resource 2–4). Clonazepam and levetiracetam 4 weeks after treatment were discontinued and there were no abnormal movement’s thereafter.
Case 2. A 54-year-old man was admitted to the hospital with dyspnea. His symptoms started with malaise, fever, myalgia, coughs, and 2 days later dyspnea. After nearly 4 days of symptoms’ onset, he developed generalized jerky movements. His voice and ocular movements were spared. Examination revealed generalized myoclonic jerks exacerbating with intentional movements and sudden noises (Online Resource 5). Chest CT showed patchy peripheral ground glass opacities and consolidations in both lungs, much more severe than case 1 (Fig. 2). Brain MRI was normal. Blood count revealed leukocytosis (WBC = 11,500) but lymphocyte count was 2300. ESR was 45 mm/h and CRP was highly positive (2+). Serum electrolytes were within normal limits. CSF analysis for cell count, protein, and glucose was normal. Nasopharyngeal and CSF RT-PCR test for COVID-19 were negative but serologic survey for both IgG and IgM in serum were positive. Treatment with levetiracetam (2000 mg/day), sodium valproate (1000 mg/day), and IVIg (100 g total) after 5 days resulted in significant resolution of myoclonic movements and he was discharged with levetiracetam and sodium valproate planned to be tapered within 1 month.
Case 3. This 52-year-old man with history of chronic lung disease came to hospital initially with dry cough, low grade fever, and headaches started 1 week earlier. His laboratory tests revealed WBC = 6600/µL, lymph = 1700/µL, ESR = 30 mm/h, and CRP = 2+ and normal serum electrolytes. Chest CT showed typical COVID-19 involvements (Fig. 3). Nasopharyngeal swab RT-PCR test was positive for COVID-19. Treatment for respiratory disease started with oseltamivir, lopinavir/ritonavir, hydroxychloroquine (hospital protocol at that time), and he was discharged after 4 days. Sixteen days after initial symptoms, he developed generalized stimulus (somatosensory and auditory) sensitive myoclonus, involving his voice as well, but not eye movements. His movements became severe and disabling after 3 days making him unable to walk. He was admitted again. Brain MRI was normal. Sodium valproate 1000 mg/day and clonazepam 1 mg qhs were beneficial, enabling him to walk with help. Chest CT was in favor of superimposed bacterial pneumonia and treatment with IV antibiotics started. He declined immunotherapy and was discharged with oral levofloxacin, sodium valproate, and clonazepam. He did not consent for taking his video but allowed anonymous data consumption for this paper. After 2-month follow-up, his movements were still present but trivial and he was still on medications.
Case 4. A 42-year-old lady visited our clinic, 10 days after initial diagnosis of COVID-19 with initial symptoms of fever, myalgia and coughs, developed jerky movements of hands and feet (more severe on right side), voice tremor, imbalance, and gait disturbance. On neurological examination, she had generalized myoclonus, dysarthria, and mild truncal ataxia similar to case 1 (but less severe). There was no prominent ocular movement involvement. Other neurological examinations were intact. Clonazepam and sodium valproate were started for abnormal movements. Unfortunately, we lost the follow-up of this patient, but we think her symptoms got improved since her respiratory and movement disorders were mild and none of our colleagues in the local area which is a small city have visited her since then.
Case 5. The other similar patient about whom we were consulted was a 44-year-old gentleman, presented with fever, chills, and 3 days later one episode of generalized tonic-clonic seizure. The same day, he developed opsoclonus, generalized stimulus sensitive and action myoclonus and ataxia, which after several days made him completely disabled and unable to sit or walk. His voice was tremulous as well (Online Resource 6–9). Chest CT was in favor of COVID-19 diagnosis (Fig. 4). Brain MRI, EEG, and CSF analysis were normal. Treatment with intravenous ceftriaxone, oral azithromycin, and anti-viral drugs Daclatasvir/sofosbuvir (Sovodak®) was instituted. With the presumed diagnosis of OMS, we started sodium valproate, clonazepam, and IVIG. After 1 week, with partial resolution of symptoms, he was discharged (see Online Resource 6–9). Follow-up at 2 months showed no abnormal movements.
Case 6. Fifty-two-year-old male nearly 1 month after initial symptoms of fever, myalgia, and cough was referred to us for treatment of abnormal movements. Neurological examination revealed generalized myoclonus with intentional component, mild ataxia, and severe shuffling gait. Voice involvement was prominent but there was no opsoclonus (Online Resource 10). Chest CT scan (Fig. 5) was in favor of COVID-19 diagnosis and nasopharyngeal swab RT-PCR test confirmed the diagnosis. CSF protein, glucose, and cell count were normal and PCR for common viral and bacterial pathogens as well as COVID-19 in CSF was negative. Serum and CSF panel for autoimmune encephalitis antibodies were negative. No oligoclonal band was detected. Treatment with clonazepam and IVIG (100 g total) resulted in significant improvement after 4 weeks (Online Resource 11).
Case 7. This very recent patient of us, a 39-year-old man, presented with fever, cough, myalgia, nausea, vomiting, and 10 days later, one episode of generalized tonic-clonic seizure. The same day, he began to suffer from jerky movements. Examination revealed prominent opsoclonus, generalized myoclonus with intentional component, and ataxia. His voice was severely involved (Online Resource 12). Chest CT was diagnostic for COVID-19 (Fig. 6). Brain CT was normal. Abnormal laboratory tests included AST = 61 U/L, ALT = 69 U/L, ESR = 58 mm/h, CRP = 75.4 mg/L. He was started on levetiracetam, clonazepam, IVIG, and dexamethasone. After 2 days, sudden increase in serum creatinine (Cr = 5) made us to stop IVIG and change levetiracetam to sodium valproate. He is still under treatment for severe respiratory involvement and acute renal failure. Clonazepam and sodium valproate alleviated myoclonus but improvement in general condition and OMS merits long-term follow-up.